In general, organisms directly contact the outside demarcated by mucous surface of digestive tracts, respiratory organs, etc. and are always exposed to the danger of invasion of microbes and foreign substances from outside. Therefore, organisms are equipped with a defense mechanism for protecting the mucous membrane. That is to say, although mucous membrane is covered with only a single layer of mucoepithelium, the epithelial cells are always covered with a viscous exocrine liquid containing mucin secreted from exocrine gland and the exocrine liquid prevents microbes and foreign substances from contacting the epithelial cells directly. In eyes, tear plays such a role and wets the surface of the eye balls.
Tear layer consists of three layers, that are oily layer, aqueous layer and mucus layer, and keratoconjunctiva epithelial cells are adjacent to the mucus layer. Mucin, which constitutes the mucus layer, is a glycoprotein mainly secreted from goblet cells of conjunctiva. It was known that mucin layer covers the surface of the hydrophobic keratoconjunctiva epithelial cells and change the property to hydrophilic ones to assist the maintenance and expansion of aqueous layer in tear whereby it plays an important role in keeping the normal structure of tear (Journal of the Eye, 8, 1037-1042(1991)).
Accordingly, if there is any substance having an action of promoting the secretion of mucin into tear fluid, it is expected that such a substance is useful to keratoconjunctiva diseases having a trouble on keratoconjunctiva epithelium such as dry eye, keratitis, conjunctivitis, corneal erosion and corneal ulcer.
Studies were made recently on the relation between drugs and production and secretion of mucin and it was reported that ebrotidine, which is a therapeutic agent for ulcer, promotes the production and secretion of rat gastric mucin (Gen. Pharmac., 24, 611-617(1993)) and that participation of mucin is presumed in an antiulcerative action of methylmethionine sulfonium chloride (Jpn. Pharmacol. Ther., 22, 4355-4361(1994)).
It was disclosed that gefarnate is a substance showing a strong antiulcerative action and is useful for therapy of peptic ulcers such as gastric ulcer and duodenal ulcer (Japanese Examined Patent Publication 28,230/1964). With regard to its function, it was reported that gefarnate promotes the deposition of acidic mucopolysaccharides on surface of a wound, to increase the amount of mucus such as hexosamine in gastric mucosa and is expected to protect the mucous membrane, etc. and to increase endogenous prostaglandins (Pharma Med., 4, 45-48(1986)).
However, there has been no report on study in ophthalmologic field.
Although various studies have been made already for therapeutic agents for keratoconjunctiva diseases including dry eye, it is a very interesting theme to find new substances which promote the production and secretion of mucin in ophthalmic tissues.